Debridement of contaminated and devitalized tissue is the first step in the surgical treatment of open extremity injuries. This event is often part of a process comprising serial debridements over the span of several days to fully assess the viability of the remaining tissue.
Penetrating trauma results in substantial bone and soft tissue loss due to the primary injury and the debridement process. For example, as a projectile or blast wave penetrates the skin, it transfers kinetic energy to the surrounding structures, which include bone, muscle, tendon, cartilage, and fat. Jussila J. Measurement of kinetic energy dissipation with gelatine fissure formation with special reference to gelatine validation. Forensic Sci Int. 2005, 150: 53-62. This energy is absorbed in the form of heat, mechanical stress, and chemical stress, and it initiates a number of events, including cell necrosis, apoptosis, and inflammation. Jussila J., Forensic Sci Int., 150: 53-62; and Jussila J, et al, Ballistic variables and tissue devitalisation in penetrating injury—establishing relationship through meta-analysis of a number of pig tests. Injury. 2005, 36:282-92.
While much of the initial damage is largely the result of necrosis and can be seen within the first twenty-four hours, delayed tissue death can result from induced programmed cell death or vascular compromise and may not be apparent for several days after the initial event. Williams A J, et al, Penetrating ballistic-like brain injury in the rat: differential time courses of hemorrhage, cell death, inflammation, and remote degeneration, J Neurotrauma, 2006, 23:1828-46. Thus, the serial tissue debridement protocol is necessary to avoid premature wound closure and to minimize the amount of retained devitalized tissue.
After debridement, the tissues are reassessed and definitive treatment is planned. The degree and nature of tissue loss determine the need for tissue-grafting or tissue substitutes that are often derived from allograft or synthetic sources. After fracture fixation and closure or coverage of open wounds, revision and reconstructive surgery is frequently required to restore the function of the injured extremity. In many instances, this may require bone and soft-tissue augmentation, lysis of adhesions (about joints and along tendons), and/or ligament reconstruction. In most cases, revision surgery stems from a need to repair or replace absent, damaged, or deranged tissues such as articular cartilage, tendon, and/or bone with use of autograft, allograft, bioengineered tissue replacement, or prosthetic materials and devices. Unfortunately, these options for tissue repair or replacement are limited by the inability of the implant to fully integrate and subsequently remodel. In addition, the inferior structural, biomechanical, and biochemical properties of the implant as compared with normal human tissue prevent full restoration of the structure-function relationship.
An essential component of all tissue-engineering construct designs is a readily available, viable, and plastic cell source. Many sources of multipotent progenitor cells (e.g., bone marrow, trabecular bone, adipose tissue, umbilical cord blood, and synovial tissue), which yield cells that have varying degrees of regenerative potential and that can be expanded in vitro, have been described. Caterson E J, et al, Human marrow-derived mesenchymal progenitor cells: isolation, culture expansion, and analysis of differentiation. Mol Biotechnol., 2002, 20:245-56; Noth U, et al, Multilineage mesenchymal differentiation potential of human trabecular bone-derived cells. J Orthop Res., 2002, 20:1060-9; Flynn A, et al, UC blood-derived mesenchymal stromal cells: an overview. Cytotherapy. 2007, 9:717-26; Boquest A C, et al, Epigenetic programming of mesenchymal stem cells from human adipose tissue, Stem Cell Rev., 2006, 2:319-29; Koga H, et al, Synovial stem cells are regionally specified according to local microenvironments after implantation for cartilage regeneration, Stem Cells, 2007, 25:689-96. However, these tissue types may not be readily available as a source of autologous multipotent cells at the time of musculoskeletal trauma.
Adult stem cells are a useful clinical resource to enhance many healing processes. One limitation, however, is the lack of availability of one's own adult stem cells without invasive surgical procedures.
Peripheral nerve injury frequently accompanies musculoskeletal trauma, which lengthens the recovery time and leads to significant dysfunction. Current treatment of peripheral nerve injuries includes primary repair, nerve autograft, or use of synthetic nerve tubes. The success of nerve repair depends primarily on the speed of axonal growth and myelination to bridge the damaged region and decrease the time to end organ re-innervation. Lee S K, et al, Peripheral nerve injury and repair, J Am Acad Orthop Surg. 8, 243, 2000.
Conventional nerve tubes contain a single lumen to guide the regenerating nerve from proximal to distal stump. Although increasing the likelihood that some axons in the nerve will reconnect with the distal end, many are unable to reconnect, and gaps larger than critical size defect are likely never to regenerate.